On the basis of their functional imaging capabilities, MRI and PET provide valuable and quantifiable data in support of tumor characterization. However, these imaging modalities are sufficiently expensive to limit their use for breast imaging and prevent their use in screening of the general population. Our long-term goal is to overcome this limitation in diagnostic breast imaging through the development and application of functional ultrasound tomography. The objective of this proposal and a first step in achieving our long-term goal is to test commercially available imaging agents in a "quick" clinical trial. The central hypothesis is that "ultrasound contrast agents, in conjunction with acoustic tomographic imaging, can characterize tumor vasculature". The hypothesis is based on a preliminary study which shows that commonly available injectable compounds propagate ultrasound signals at much higher or much lower sound speeds compared to human tissue, suggesting that the visibility of tumors can be further enhanced and characterized. The proposed study will test the hypothesis through off-label use of commercially available imaging agents. The rationale for this study is that a successful outcome would lay the foundation for future larger studies of functional ultrasound imaging to assess the clinical benefits of improved detection and characterization of tumors, especially in denser breasts. The following specific aims will guide our study. Aim #1: Evaluate performance of commercially available contrast agents. Our working hypothesis is that some commercial contrast agents will measurably increase the contrast of tumors relative to background tissue by enhancing their acoustic differences. The hypothesis will be tested by measuring in-vivo tumor enhancement differences between the various agents in a small cohort of patients using a recently developed imaging prototype. Aim #2: Demonstrate functional imaging for mass detection and characterization Our working hypothesis is that, similarly to dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and Breast Specific Gamma Imaging (BSGI) cancers produce a uniquely different kinematic profile relative to benign masses. We will test this hypothesis by measuring time-dependent acoustic signatures of breast masses from one group of patients with cancer and one with benign findings. PUBLIC HEALTH RELEVANCE: The proposed research paves the way for functional tomographic imaging, an ultrasound modality that currently does not exist. The clinical implications of such capabilities are immense because functional ultrasound tomography has the potential to provide MRI- like capability at a small fraction of the cost. Such a development would facilitate alternative screening of high risk women, as is now being proposed for MRI. Improved sensitivity to tumors would also pave the way for screening of the general population by overcoming MRI's cost barrier to universal screening.